| Objectives:Breast cancer is endocrine-related cancer with high incidence and mortality rates in women worldwide.By 2020,the number of breast cancer cases and deaths expected in the world has surpassed that of lung cancer.At this point,breast cancer has replaced lung cancer and become the largest cancer in the world.Studies have found that the incidence of breast cancer and family history is highly related.Other factors such as early menarche,late menopause,late age of first pregnancy and low number of births that can increase the risk of breast cancer;Unhealthy lifestyles,such as excessive alcohol consumption and excessive dietary fat intake,also increase the risk of breast cancer.China has a low incidence of breast cancer,but since the 1990s its incidence has increased more than twice as fast as have global rates,particularly in urban areas.So far,the treatment of breast cancer is mainly divided into systemic therapy and local therapy,systemic therapy includes endocrine therapy and chemotherapy,since most drugs can not only play an anti-tumor role but also has toxicities in a higher dose,thus,toxicities are especially important considerations.The existence of drug resistance leads to the effectiveness of systemic treatment the recurrencerate was high.Local therapy mainly include surgery and radiotherapy.There are many contraindications in surgery,and the two therapy can not be used together.After surgery,there will be a variety of complications.Based on these situation,it is urgent to develop a low-dose treatment with low toxicity,and few side effects,as well as inhibiting the growth and recurrence of breast cancer.In this study,we construct an efficient nano drug delivery system with self polymerized diblock copolymer PEG-PLGA as carrier and co-delivery of paclitaxel and curcumin,so as to achieve the purpose of treating breast cancer with low dose and high safety in vivo.Methods:In this study,PTX/CUR-NPs were prepared by anti solvent precipitation method,PTX-NPs and CUR-NPs were prepared by the same method and drug dose respectively for comparison.In order to characterize nanoparticals,PTX/CUR-NPs,PTX/CUR-NPs、PTX-NPs and CUR-NPs were tested by particle size potential,stability and Fourier transform infrared spectroscopy respectively,which proved the successful preparation of nanoparticles.The TEM images of PTX/CUR-NPs were also examined to prove the basic shape of PTX/CUR-NPs.The release of PTX and CUR from PTX/CUR-NPs was measured in vitro.The inhibitory effects of PTX/CUR-NPs,PTX-NPs,CUR-NPs,PTX and CUR of MDA-MB-231 and 4T1 tumor cells were detected by MTT assay.Moreover,the uptake of PTX/CUR-NPs in cells was detected by using the fluorescence characteristics of CUR.Furthermore,The in vivo experiments were carried out when the mean tumor volume reached approximately 40 mm3.The mice were divided into seven groups.The safety of PTX/CUR-NPs was proved by body weight record,organ index and H&E staining of tissue sections.Results:The particle size of PTX/CUR-NPs was 85.7±1.35 nm,the polydispersity coefficient was 0.168±0.026,and the zeta potential was-2.98±1.26 MV.The TEM images were uniform and round.The drug loading of PTX/CUR-NPs for paclitaxel was 31.59±0.528,the entrapment efficiency was 82.77±1.39;the drug loading of curcumin was 21.78±0.23,and the entrapment efficiency was 85.6±0.88.In vitro,PTX and CUR were released rapidly and then slowlyi in mediam not only PH=7.5 but also PH=5.4.PTX/CUR-NPs could inhibit the growth of both MDA-MB-231 and 4T1 cells,beside PTX/CUR-NPs had more uptake in tumor cells than free paclitaxel and curcumin.In vivo test proved that PTX/CUR-NPs had inhibitory effect on breast cancer,and the weight of mice continued growning during the treatment.That improves there was no significant difference in organ index,H&E staining of heart,liver,spleen,lung and kidney between each group and the control group,which further proved the safety of PTX/CUR-NPs.So far,PTX/CUR-NPs is an effective and less toxic drug for breast cancer. |
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